rs1364129144

Variant names:

• chr4-142112558-G-T
• rs1364129144
• NM_001101669.3:c.2260C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001101669.3(INPP4B):​c.2260C>A​(p.Gln754Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,460,686 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: INPP4B NM_001101669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.59
• Publications: 0 publications found

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101669.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	NM_001101669.3	MANE Select	c.2260C>A	p.Gln754Lys	missense	Exon 22 of 26	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.2260C>A	p.Gln754Lys	missense	Exon 22 of 26	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.2260C>A	p.Gln754Lys	missense	Exon 21 of 25	NP_001372264.1	E7EQN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	ENST00000262992.9	TSL:5 MANE Select	c.2260C>A	p.Gln754Lys	missense	Exon 22 of 26	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.2260C>A	p.Gln754Lys	missense	Exon 21 of 25	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.2260C>A	p.Gln754Lys	missense	Exon 23 of 27	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250622 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1460686 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726618

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.000135 AC: 6 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111408

Other (OTH) AF: 0.0000166 AC: 1 AN: 60316

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		8.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.29
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.47		Gain of ubiquitination at Q754 (P = 0.0177)
MVP		0.36
MPC		0.85
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.52
gMVP		0.85
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1364129144; hg19: chr4-143033711;